Uroporphyrinogen decarboxylase (UROD)

Uroporphyrinogen decarboxylase (UROD) is a homodimeric enzyme that catalyzes the fifth step in the heme biosynthetic pathway, converting uroporphyrinogen III into coproporphyrinogen III via decarboxylation of four acetate side chains[1][2][4]. This step is essential for cellular heme production and iron homeostasis. UROD is notable for operating without any cofactors, utilizing substrate protonation for its catalytic mechanism[1][5]. Deficiency or mutations in UROD cause porphyria cutanea tarda and hepatoerythropoietic porphyria, disorders characterized by porphyrin buildup and skin photosensitivity. UROD has also been studied as a potential cancer therapy target, particularly to sensitize tumors to radiotherapy by altering cellular heme metabolism[3]. Emerging drug candidates from virtual screening, such as isopraeroside IV, scopolin, and nodakenin, act as putative enzyme inhibitors. UROD activity and mutation status serve as clinical biomarkers for porphyria diagnosis and treatment selection[1][3].

Other names

Uroporphyrinogen III decarboxylaseURO-DUPDPCTuroporphyrinogen decarboxylaseuroporphyrinogen III decarboxylase

Competitive and allosteric inhibition of enzyme activity (for small molecule inhibitors); Sensitization to radiotherapy via heme biosynthesis modulation